Our aged population is growing; by 2030 it is predicted that 1 out of every 5 people will be over the age of 65. It is well known that aging is associated with multiple functional declines that can lead to a loss of independence. Cognitive declines, particularly in learning and memory, are seen as early as the 5th decade of life in humans. The candidate, Dr. Kathy Magnusson, has over 23 years of experience in utilizing the Morris water maze to examine the molecular mechanisms underlying age-related cognitive decline in rodents. This body of research clearly demonstrates the importance of the prefrontal cortex in age-related declines in spatial memory in mice, including showing that older mice recruit additional prefrontal regions to perform the same spatial learning task as young. The mentor, Dr. Scott Moffat, has evidence that changes in the prefrontal cortex during aging in humans are involved in spatial memory. However, the most direct functional MRI measures were not done with a human analog of the water maze task. NIH's OppNet has identified a critical need for researchers in the basic behavioral and social sciences to be cross-trained in both animal and human research in order to enhance translational research (RFA-DA-14-002). The candidate's immediate goals are to adapt a virtual water maze task for humans to more closely resemble the mouse task and to learn functional imaging methods in humans. The long-term goals are to establish a long-term collaboration with the mentor to examine the role of prefrontal cortex in spatial memory and develop interventions into age-related cognitive decline that will translate from rodent models to humans. The mentor has extensive experience with human cognitive testing, functional imaging and replicating animal models in studies of human cognitive aging. Georgia Institute of Technology has all of the facilities and equipment necessary to train the candidate and conduct a pilot project. The synergy between the research interests of the candidate and mentor and the excellent facilities at the mentor's institution make this an ideal fit for accomplishing OppNet's goals to cross-train behavioral scientists and establish collaborations in cross-species research. Developing an animal model of brain region recruitments would help determine whether this is beneficial or harmful to memory in the elderly. Although both labs have evidence for prefrontal recruitment, the studies used different tasks. Our central hypothesis is that deficits in performance of a spatial long-term memory task during aging in humans are partially due to alterations in activation of prefrontal regions. This will be addressed by Aim 1: To identify activations and deactivations of brain regions that show relationships to spatial memory performance in young and old humans performing in a water maze task. These studies will provide important proof of principle that aged humans and rodents show similar recruitment of additional brain regions when performing a similar task. Being able to cross-experiment with both rodents and humans will enable us to better study mechanisms underlying this recruitment and design, test and apply interventions to improve cognitive flexibility into old age.